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二羟丙酮诱导 A375P 黑素瘤细胞 G2/M 期阻滞和凋亡性细胞死亡。

Dihydroxyacetone induces G2/M arrest and apoptotic cell death in A375P melanoma cells.

机构信息

Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Ave, Mobile, Alabama, 36604-1405.

Auburn University, Harrison School of Pharmacy, University of South Alabama, 650 Clinic Dr, Mobile, Alabama, 36608.

出版信息

Environ Toxicol. 2018 Mar;33(3):333-342. doi: 10.1002/tox.22520. Epub 2017 Nov 29.

Abstract

The active ingredient in sunless tanning products (STPs) is a simple sugar, dihydroxyacetone (DHA). Several studies have demonstrated that DHA is absorbed within the viable layers of skin and not fully contained within the stratum corneum. Additionally, spray tanning and other aerosolized application methods have increased the risk of internal exposure through mucous membranes and inhalation. Beyond its presence in STPs, DHA also occurs as an endogenous by-product of fructose metabolism, and an excess of DHA in cells can induce advanced glycation end (AGE) products and oxidative stress. Therefore, exogenous and endogenous exposures to DHA may be harmful to cells, and it has already been demonstrated that exogenous exposure to DHA is cytotoxic in immortalized keratinocytes. Still, little is known about the exogenous DHA exposure effects on other skin components. In this study, we explore the effects of exogenous DHA exposure in a human melanoma cell line, A375P. Melanoma cells were sensitive to DHA and displayed a transient burst of reactive oxygen species within an hour of exposure. Cell cycle arrest at G2/M was observed within 24 h of exposure, and apoptosis, monitored by the cleavage of PARP-1 and Caspase-3, was detected within 72 h of exposure to DHA. Together, these demonstrate that exogenous exposure to DHA has cytotoxic effects in our selected cell model and indicates the need to further investigate the exogenous exposure effects of DHA in other relevant exposure models.

摘要

日光浴产品(STP)中的活性成分是一种简单的糖,即二羟丙酮(DHA)。多项研究表明,DHA 被皮肤的活层吸收,而不完全包含在角质层中。此外,喷雾晒黑和其他气溶胶应用方法通过黏膜和吸入增加了内部暴露的风险。除了存在于 STP 中,DHA 还作为果糖代谢的内源性副产物出现,细胞内过多的 DHA 会诱导晚期糖基化终产物(AGE)和氧化应激。因此,外源性和内源性暴露于 DHA 可能对细胞有害,并且已经证明外源性暴露于 DHA 在永生化角质细胞中具有细胞毒性。尽管如此,人们对其他皮肤成分的外源性 DHA 暴露效应知之甚少。在这项研究中,我们在人黑色素瘤细胞系 A375P 中探索了外源性 DHA 暴露的影响。黑色素瘤细胞对 DHA 敏感,并在暴露后一小时内显示出活性氧的短暂爆发。暴露 24 小时内观察到细胞周期停滞在 G2/M 期,并且在暴露于 DHA 的 72 小时内通过 PARP-1 和 Caspase-3 的裂解检测到细胞凋亡。总之,这些表明外源性暴露于 DHA 在我们选择的细胞模型中具有细胞毒性作用,并表明需要进一步研究 DHA 在其他相关暴露模型中的外源性暴露效应。

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